Endobronchitis has been used as a model of mucosal immunology and more specifically to reflect a particular balance of the host-parasite relationship at the mucosal surface. The normally sterile bronchus mucosa becomes colonised by “avirulent” bacteria which do not generally invade. Most prominent is non-typable Haemophilus influenzae (NTHI). Acute episodes of infection in subjects with chronic lung disease are thus likely to be initiated by events which disturb a finely balanced relationship between colonising bacteria and the bronchus mucosa. The restraining host response involves Th1 T cells (which produce γ interferon), which operate by recruiting and activating neutrophils within the bronchus mucosa. If excessive and/or inappropriate, this process leads to increase cough and purulent sputum, the hallmark of “acute bronchitis” in subjects with established chronic lung disease.
The original oral vaccine used killed NTHI to activate the common mucosal system to enhance release of lymphocytes (then considered to be antibody producing B lymphocytes) from the Payer's patches along the small intestine, which relocated within the bronchus mucosa, producing IgA antibody which would prevent descent of bacteria into the bronchi. This concept has been superseded. This vaccine requires that (i) a single bacterial content and (ii) no added adjuvant. The absence of adjuvant was thought necessary to avoid the then considered restrictions imposed by the highly downregulated mucosal environment, ie additions of adjuvant to a simple single bacterial vaccine would enhance mucosal downregulation, reduce vaccine effectiveness, and even promote or exacerbate infection.
It is an object of the present invention to overcome or at least ameliorate one or more of the limitations of the prior art or to provide a useful alternative.